Glyoxal acid-free (GAF) histological fixative is a suitable alternative to formalin: results from an open-label comparative non-inferiority study.

Formalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histological samples for over a century. Despite its considerable advantages, growing evidence points to objective toxicity, particularly highlighting its carcinogenicity and mutagenic effects. In 2016, the European Union proposed a ban, but a temporary permission was granted in consideration of its fundamental role in the medical-diagnostic field. In the present study, we tested an innovative fixative, glyoxal acid-free (GAF) (a glyoxal solution deprived of acids), which allows optimal tissue fixation at structural and molecular level combined with the absence of toxicity and carcinogenic activity. An open-label, non-inferiority, multicentric trial was performed comparing fixation of histological specimens with GAF fixative vs standard phosphate-buffered formalin (PBF), evaluating the morphological preservation and the diagnostic value with four binary score questions answered by both the central pathology reviewer and local center reviewers. The mean of total score in the GAF vs PBF fixative groups was 3.7 ± 0.5 vs 3.9 ± 0.3 for the central reviewer and 3.8 ± 0.5 vs 4.0 ± 0.1 for the local pathologist reviewers, respectively. In terms of median value, similar results were observed between the two fixative groups, with a median value of 4.0. Data collected indicate the non-inferiority of GAF as compared to PBF for all organs tested. The present clinical performance study, performed following the international standard for performance evaluation of in vitro diagnostic medical devices, highlights the capability of GAF to ensure both structural preservation and diagnostic value of the preparations.

Blood pressure, glycemic status and advanced liver fibrosis assessed by transient elastography in the general United States population.

OBJECTIVE: Few studies investigated the role of different predictors of advanced liver fibrosis in unselected populations. Here, we estimate the prevalence of steatosis and fibrosis in the general United States population by means of transient elastography and evaluate the impact of blood pressure (BP) and diabetes on disease severity. METHODS: This is a cross-sectional study of United States adults participating in the 2017-2018 cycle of the National Health and Nutrition Examination Survey. Participants underwent a transient elastography examination, and liver steatosis and fibrosis were estimated through the controlled attenuation parameter (CAP) score and liver stiffness measurement (LSM), respectively. RESULTS: Four thousand, three hundred and seventy-one participants had reliable transient elastography and BP readings. Steatosis (CAP ≥ 248 dB/m), advanced fibrosis (LSM ≥ 9.6 kPa) and cirrhosis (LSM ≥ 13 kPa) were present in 56.9, 5.5 and 2.9% of participants, respectively. After controlling for potential confounders, risk of steatosis increased proportionally going from participants with optimal (reference) to those with normal [odds ratio (OR) 1.24, 95% confidence interval (CI) 0.83-1.86], high normal (OR 1.41, 95% CI 1.01-1.97) and elevated BP (OR 1.64, 95% CI 1.21-2.21), whereas no significant association was found between BP status and liver fibrosis. Conversely, presence of diabetes increased the risk of both steatosis (OR 2.15, 95% CI 1.49-3.11) and advanced fibrosis (OR 2.25, 95% CI 1.36-3.72). CONCLUSION: Liver steatosis and fibrosis are highly prevalent in the multiethnic United States adult population, raising concerns for future incidence of cirrhosis and its complications. BP status was associated with a progressively higher risk of steatosis, whereas obesity and diabetes were consistently associated with both steatosis and fibrosis.

Lack of awareness of liver organ damage in patients with type 2 diabetes.

AIMS: Liver steatosis, a typical finding in patients with type 2 diabetes (T2D), can lead to cirrhosis and hepatocellular carcinoma. The aim of the present study is to estimate the awareness of liver disease among patients with T2D and whether it differs according to the degree of liver fibrosis estimated by transient elastography (TE). METHODS: This is a population-based cross-sectional study. We included all patients with T2D that participated in the 2017-2018 cycle of the National Health and Nutrition Examination Survey and underwent a TE examination. Presence of liver steatosis and fibrosis was assessed by the median values of controlled attenuation parameter and liver stiffness measurement, respectively. RESULTS: Among the 825 patients included in the analysis, 8.1% (95% CI 5.1%-12.7%) of patients with steatosis were aware of having a liver condition. Even if awareness increased proportionally with increasing severity of organ damage, it remained limited even among patients with advanced fibrosis (17.9%, 95% CI 8.8%-33.3%). CONCLUSIONS: Despite increasing evidence of a frequent hepatic involvement associated with poor prognosis, awareness of suffering of advanced liver disease in patients with T2D is remarkably low, likely reflecting little recognition also among the team of health care professionals.

Prevalence of Liver Steatosis and Fibrosis Detected by Transient Elastography in Adolescents in the 2017-2018 National Health and Nutrition Examination Survey.

BACKGROUND & AIMS: Metabolic-associated fatty liver disease (MAFLD) is common among adolescents, but the prevalence of significant fibrosis in this age group is not known. We aimed to estimate the prevalence of MAFLD and significant (≥F2) fibrosis by transient elastography (TE) in adolescents in the United States. METHODS: We analyzed TE data from participants 12-18 years old included in the National Health and Nutrition Examination Survey 2017-2018 (data available from 867 adolescents). Steatosis was evaluated by the median controlled attenuation parameter (CAP) and fibrosis by median liver stiffness measurement. RESULTS: Two-hundred forty participants (24.16%; 95% CI, 21.07-27.24) had any degree of steatosis (CAP≥248 dBm), 123 participants (11.6%; 95% CI, 9.19-14.06) had S3 steatosis (CAP≥280 dBm), and 51 participants (4.4%; 95% CI, 2.51-6.33) had significant fibrosis (liver stiffness ≥7.4 kPa). Multivariate analyses revealed that body mass index (odds ratio [OR] per unit increase, 1.2; 95% CI, 1.2-1.4), sex (OR female vs male participants , 0.5; 95% CI, 0.4-0.7), ethnicity (OR, Hispanic vs non-Hispanic white, 4.5; 95% CI, 1.7-11.8), and hypertension (OR, 3.5; 95% CI, 1.3-9.9) were associated with S3 steatosis, whereas body mass index (OR, 1.1 per unit increase; 95% CI, 1.0-1.2) and ethnicity (OR, non-Hispanic black vs non-Hispanic white, 3.9; 95% CI, 1.2-13.2) were associated with significant fibrosis. High proportions of participants with fibrosis were in the normal weight category (35%) and had normal levels of alanine aminotransferase (78%). CONCLUSIONS: Prevalence of MAFLD and significant fibrosis are alarmingly high in adolescents in the National Health and Nutrition Examination Survey 2017-2018. Levels of alanine aminotransferase and blood biomarkers do not correctly identify adolescents with more advanced disease. Effective noninvasive strategies to differentiate simple steatosis from progressive forms are urgently needed.

High Prevalence of Advanced Liver Fibrosis Assessed by Transient Elastography Among U.S. Adults With Type 2 Diabetes.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is an important risk factor for the progression of metabolic liver disease to advanced fibrosis. Here, we provide an estimate of the prevalence of steatosis and fibrosis in U.S. adults with T2DM on the basis of transient elastography (TE) and identify factors associated with these conditions. RESEARCH DESIGN AND METHODS: This is a cross-sectional study of U.S. adults with T2DM participating in the 2017-2018 cycle of the National Health and Nutrition Examination Survey who were evaluated by TE. Hepatic steatosis and fibrosis were diagnosed by the median value of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), respectively. RESULTS: Among the 825 patients with reliable TE examination results, 484 (53.7%) were assessed using the M probe and 341 (46.3%) using the XL probe. Liver steatosis (CAP ≥274 dB/m), advanced fibrosis (LSM ≥9.7 kPa), and cirrhosis (LSM ≥13.6 kPa) were present in 73.8% (95% CI 68.5%-78.5%), 15.4% (95% CI 12.2%-19.0%), and 7.7% (95% CI 4.8%-11.9%) of patients, respectively. The mean ± SE age of patients with advanced fibrosis and cirrhosis was 63.7 ± 2.2 years and 57.8 ± 1.6 years, respectively. In the multivariable logistic regression model, BMI, non-Black race, and ALT levels were independent predictors of steatosis; and BMI, non-Black race, and AST and γ-glutamyltranspeptidase levels were independent predictors of advanced fibrosis. CONCLUSIONS: Prevalence of both liver steatosis and fibrosis is high in patients with T2DM from the United States and obesity is a major risk factor. Our results support the screening of these conditions among patients with diabetes.

Nonalcoholic Fatty Liver Disease and Advanced Fibrosis in US Adults Across Blood Pressure Categories.

Nonalcoholic fatty liver disease (NAFLD) is common in patients with hypertension but controversy exists as to whether screening for this condition should be performed. Here, we evaluate the prevalence of NAFLD and advanced fibrosis in US adults across blood pressure categories and estimate the number of patients who require referral to hepatologists. In this cross-sectional analysis of 11 489 adults from the 2005 to 2016 National Health and Nutrition Examination Survey, participants were segregated as having optimal, normal, high normal, and elevated blood pressure according to the 2018 European Society of Cardiology/Hypertension guidelines. NAFLD was defined using the US fatty liver index, whereas fibrosis was assessed using the NAFLD fibrosis score, fibrosis-4, and Hepamet Fibrosis Score. NAFLD prevalence increased progressively from optimal (16.5%) to normal (34.5%), high normal (39.9%), and elevated blood pressure (50.2%, P<0.001). Patients with hypertension also showed a higher prevalence of advanced fibrosis (3%-9%, based on the specific biomarker used). When the screening flowchart from the European Association for the Study of the Liver, Diabetes, and Obesity guidelines was applied to patients with hypertension, 26.7% needed referral to hepatologists. Risk of referral was higher in Hispanic patients and those with diabetes mellitus, heart failure, and an altered urinary albumin excretion. NAFLD is highly prevalent in US adults with hypertension and a quarter of them would need to be referred to hepatologists because of a high risk of advanced fibrosis. While future studies on cost-effectiveness are needed, screening for NAFLD in these patients could be beneficial.